The Role of Perineural Invasion in Prostate Cancer and Its Prognostic Significance

SIMPLE SUMMARY: Prostate cancer is one of the most frequently diagnosed cancers in men worldwide. Perineural invasion (PNI), the movement of cancer cells along nerves, is a commonly observed approach to tumor spread and is important in both research and clinical practice of prostate cancer. However, despite many studies reporting on molecules and pathways involved in PNI, understanding its clinical relevance remains insufficient. In this review, we aim to summarize the current knowledge of mechanisms and prognostic significance of PNI in prostate cancer, which may provide new perspectives for future studies and improved treatment. ABSTRACT: Perineural invasion (PNI) is a common indication of tumor metastasis that can be detected in multiple malignancies, including prostate cancer. In the development of PNI, tumor cells closely interact with the nerve components in the tumor microenvironment and create the perineural niche, which provides a supportive surrounding for their survival and invasion and benefits the nerve cells. Various transcription factors, cytokines, chemokines, and their related signaling pathways have been reported to be important in the progress of PNI. Nevertheless, the current understanding of the molecular mechanism of PNI is still very limited. Clinically, PNI is commonly associated with adverse clinicopathological parameters and poor outcomes for prostate cancer patients. However, whether PNI could act as an independent prognostic predictor remains controversial among studies due to inconsistent research aim and endpoint, sample type, statistical methods, and, most importantly, the definition and inclusion criteria. In this review, we provide a summary and comparison of the prognostic significance of PNI in prostate cancer based on existing literature and propose that a more standardized description of PNI would be helpful for a better understanding of its clinical relevance.